Homoharringtonine (HHT), also known as O-3-[(2R)-2,6-dihydroxy-2-(2′-methoxy-2′-oxoethyl)-6-methylheptanoyl]cephalotaxine, is an alkaloid extracted and separated from Chinese herbal plants of Cephalotaxaceae family, in particular from cephatotaxus fortuneif or congeners thereof. Cephatotaxus genus plants of the Cephalotaxaceae family consist of 9 species, 8 of which are originated in China. Plants of this genus contain a plurality of alkaloids, in which harringtonine, homoharringtonine, isoharringtonine and deoxyharringtonine have been extracted, identified and extensively investigated [ZHONG Sanbao et al., Studies on Semi-synthesis of Cephalotaxine Esters and Correlation of Their Structures with Antitumor activity, Acta Pharmaceutica Sinica, 1994, 29 (1), 33-39; WANG Dingzhi et al., Studies on Alkaloids in Cephatotaxus genus Plants, Acta Pharmaceutica Sinica, 1992, 03, 178-184]. Furthermore, a non-ester alkaloid (i.e. cephalotaxine) is also separated from Cephatotaxus as a main component.

Clinical studies demonstrate that HHT can be applied in the remission induction and post-remission treatment of acute myeloid leukemia, in the treatment of myelodysplastic syndrome (MDS), chronic myelogenous leukemia, polycythemia vera and malignant lymphoma, etc., particularly in the treatment of acute non-lymphocytic leukemia [ZHANG, Zhixue et al., Clinical study of HAG projects for the treatment of middle and high risk myeloid hyperplasia singular syndrome and acute myeloid leukemia, Journal of Jinggangshan University, 2010, 31(6),108-110; DENG, Jianqun et al., The impact of homoharringtonine to leukemia proto-oncogene bcl-2, c-myc, tumor suppressor gene p15, Chin J of Clinical Rational Drug Use, 2010, 3(7), 15-16; CHEN, Lijuan et al., A Study of Apoptosis on Non-lymphocytic Leukemia Cells Induced by Cytosine Arabinoside and Homoharringtonine, Jiangsu Medical Journal, 1999, 25(4), 257-258; ZHANG, Hui et al., 27 clinical analysis of LD-HA regimen in the treatment of acute myeloid leukemia, Acta Academiae Medicinae Suzhou, 1997, 17(4), 689-690; DING, Suxin et al., 26 clinical analysis of LD-HA regimen in the treatment of hypoplastic leukemia, Acta Academiae Medicinae Suzhou, 1997, 17(1), 89-90; XUE, Yanping et al., Clinical observation of HAD regimen in the treatment of adult acute non-lymphocytic leukemia, Chinese Journal of Hematology, 1995, 16(2), 59-61].
HHT can promote cell differentiation and apoptosis [WANG Yun et al., Experimental study of K562 and CML cell apoptosis and differentiation induced by homoharringtonine, Shanghai Medical Journal, 2001, 24(3), 166-168; LU, Dayong et al., Effect of homoharringtonine on leukemia cell differentiation and tumor metastasis, Journal of Shanghai University, 1999, 5(2), 175-177].
According to the studies on the synchronous KB (human oral epidermoid carcinoma) cells, HHT possesses cell cycle specificity and has the strongest killing effect on the cells in G1 and G2 phases and a relatively weaker effect on cells in S phase [JIN, Wei et al., Studies on the effect of homoharringtonine on HL-60 cells and QCY7703 cells, Acta Chinese Medicine and Pharmacology, 2001, 29(3), 44-45; LUO, Chenmei et al., Effect of homoharringtonine and Xueshuantong on human pterygium fibroblasts cell cyclic variation, Journal of Traditional Chinese Ophthalmology, 1999, 9(2), 67-70].
The pharmacological effects of HHT are mainly in inhibiting the protein synthesis of the eukaryotic cells, inhibiting the binding of aminoacyl-tRNA to riboses and the formation of the ribosomes thereof and peptide chains, thereby affecting the early stages of polymer formation, and causing the polyribosomes to disaggregate, interfering ribosomal protein functions, and also inhibiting the synthesis of intracellular DNAs [CAI, Zhen et al., Involvement of apoptosis-related gene Survivin, bcl-2 and bax in the homoharringtonine-induced apoptosis of myelodysplastic syndrome cell line(MUTZ-1), Journal of Practical Oncology, 2003, 18(3), 188-191; CAI, Zhen et al., Expression of survivin mRNA in HHT-induced cell apoptosis of hematological malignancy cell lines, Journal of Zhejiang University, 2006, 35(2), 204-208; WANG, Hengxiang et al., Homoharringtonine Induces Apoptosis of K562 Cells through Inhibition of P210bcr/abl, Chinese Journal of Experimental Hematology, 2000, 8(4), 287-289; CHEN, Chunyan et al., Comparative proteomics research of apoptosis initiation induced by homoharringtonine in HL-60 cells, Chinese Journal of Hematology, 2003, 24(12), 624-628; LI, Yufeng et al., Effect of homoharringtonine on the telomerase activity of bone marrow CD34+ cells in patients of chronic myeloid leukemia, Journal of Leukemia-Lymphoma, 2004, 13(1), 42-43; LI, Yufeng et al., Effect of homoharringtonine on bone marrow CD34−+CD7−+cells in patients of chronic myeloid leukemia, Chinese Journal of Hematology, 2007, 28(10), 706-707; LI, Yufeng et al., Effect of homoharringtonine on T and Th lymphocytes subsets in patients of chronic myeloid leukemia, Leukemia-Lymphoma, 2006, 15(1), 37-39; LI, Yufeng et al., Effect of homoharringtonine on the telomerase activity of bone marrow cells and K562 cells in patients of chronic myeloid leukemia, Chinese Journal of Hematology, 2003, 24(6), 329-329; MENG, Xiaoli, Effects of homoharringtonine on telomerase activity in HL60 cells, Journal of Zhengzhou University, 2004, 39(3), 440-442; XIE, Wanzhuo et al., Effect of telomerase in homoharringtonine-induced apoptosis of HL-60 cells, Chinese Journal of Medical Genetics, 2002, 19(2), 169-171].
On the other hand, aminated or amidated small molecules have been widely applied in pharmaceutical research, development and applications. However, reports on the synthesis and application of aminated or amidated homoharringtonine derivatives have not yet been seen.